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In Brief | Paediatrics & Neonatology


Increased Seizure Risk in Children Linked to First-Generation Antihistamines: Findings from a Nationwide Cohort Study


Time to read: 02:04
Time to listen: 04:43
 
Published on MedED:  24 September 2024
Originally Published: 28 August 2024
Sourced: JAMA Network Open
Type of article: In Brief
MedED Catalogue Reference: MpIB0013
Category: Paediatrics & Neonatology
Cross Reference: Neurology
Keywords: paediatrics, neurology, seizure, anti-histamine
 
Key Takeaway
First-generation antihistamines are associated with a significantly increased risk of seizures in children, particularly in those aged 6 to 24 months. Caution is advised when prescribing these medications to pediatric populations.
 
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Originally published in JAMA Network Open, 28th August 2024
 
 
Despite reduced therapeutic use due to poor selectivity and interactions with other receptors, first-generation antihistamines remain widely prescribed for managing rhinorrhoea—particularly from the common cold—and pruritus in children.

Numerous studies have demonstrated that first-generation antihistamines can impact brain wave activity, increase seizure susceptibility, and alter electroencephalographic (EEG) patterns in individuals predisposed to seizures. Animal studies have linked H1 antihistamines to an increased seizure risk, and clinical reports have identified antihistamines as triggers for acute symptomatic seizures.
 
Caution is advised when prescribing these agents to children under two years, as the full impact of first-generation antihistamines on brain wave activity, particularly in younger and more vulnerable age groups, remains underexplored.
 
In a recent study published in JAMA Network Open, researchers Kim JH, Ha EK, Han B, et al. investigated the association between first-generation antihistamines and seizure risk in young children using a population-based dataset. The primary outcome was an index seizure event, with the date of this seizure event referred to as the index date.
 
The cohort study employed a self-controlled case-crossover design to compare first-generation antihistamine prescriptions from 15 days before the index date—termed the hazard period—with prescriptions from two control periods: 31 to 45 days prior (control period 1) and 61 to 75 days prior (control period 2), both of which were deemed unrelated to seizures.
 
The findings were as follows:
 
Out of 11,729 children who experienced a seizure event, 3,178 were prescribed antihistamines during either the hazard or control period, but not both.
 
• 55.9% of the seizure events occurred in boys (1,776 of 3,178).
• 31% of the events were in children aged 6 to 24 months (985 events).
• 45.5% were recorded in children aged 25 months to 6 years (1,445 events).
 
During the hazard period, there were 1,476 first-generation antihistamine prescriptions recorded, compared to 1,239 prescriptions during control period 1, and 1,278 prescriptions during control period 2.
 
After adjusting for multiple confounders, first-generation antihistamine prescriptions were associated with a 22% increased risk of seizure events during the hazard period (adjusted odds ratio [AOR], 1.22).
 
Subgroup analyses revealed:
 
• A higher risk in children aged 6 to 24 months prescribed first-generation antihistamines (AOR, 1.49).
• A lower risk in children aged 25 months to 6 years (AOR, 1.11).

Sensitivity analyses, which included adjustments for exposure window periods, evaluation of new prescriptions, comparison with control points from the same period a year prior, and exclusion of individuals on combination drugs, confirmed a similarly elevated risk.

The study underscores the need for cautious prescribing practices, particularly for young children, and highlights the importance of further research to clarify the relationship between antihistamine use and seizure events.


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